Transdermal drug delivery systems (TDDS) involve two major categories of products, namely transdermal (TD) patches and topical composition. TD patches have a well-defined contact area with the skin of a patient that will allow accurate administration of the drug from the drug-containing medium on the patch to the user through his/her skin. In addition, the drug delivery medium of the patch is protected when in use. Important TD patches that are commercially available include Duragesic® (fentanyl as active ingredient), Lidoderm (lidocaine as active ingredient) and Burtrans® (buprenorphine as active ingredient) for management of pain, Ortho Evra (ethinyl estradiol and norelgestromin as active ingredients) for contraceptive use, Daytrana® (methylphenidate as active ingredient) for attention deficient/hyperactivity disorder (ADHD), and Neupro® (rotigotine as active ingredient) for Parkinson's disease.
Most of the topical composition products are applied to a certain area of the skin and are intended to affect only the area to which they are applied. Commercially available examples include Emla® as a local anesthetic cream (lidocaine and prilocaine as active ingredients), Pennsaid solution (diclofenac as active ingredient) for pain caused by osteoarthritis, and Lotrisone cream (betamethasone and clotrimazol as active ingredients) for reducing itching, swelling, and redness of the skin. An exception is Elestrin gel (estradiol as active ingredient), which is an example of transdermal drug delivery using a topical formulation 7, for vasomotor symptoms (hot flash) due to menopause. But in general, topical composition products lack the mechanisms in controlling rate of drug delivery through a fixed area of the user's skin.
There are important advantages by taking the transdermal route for drug delivery when compared with the more conventional routes. One of them is the avoidance of hepatic first-pass metabolism. The other is simple discontinuation of medication if needed. An obvious disadvantage is that only very limited number of active pharmaceutical ingredients (API) are suitable for transdermal delivery.
Commercial manufacturing for products of TD patches requires sophisticated equipment and can be costly as compared with topical composition products. But TD patches offer much more accurate rate of drug delivery when compared with topical composition products. The delivery system in this invention combines the advantage of accurate drug delivery from a TD patch, and the advantages of topical composition product, which includes low cost in manufacturing and ease of use. A good example for application of the applicator/topical formulation combination is ibuprofen in a topical formulation 7 on the applicator 6 for reducing fever in infants and toddlers.
Ibuprofen is a nonsteroidal anti-inflammatory drug (NSAID) used widely for relieving pain, helping with fever, and reducing inflammation. One of the side effects for ibuprofen is gastrointestinal ulceration/bleeding, which can be avoided if it is administered trans-dermally. It is estimated that 20% of the pediatric emergency visit is related to fever (Alpern E R, Henretig F M. Fever. Fleisher G R, Ludwg S, Henretig F M, eds. Textbook of Pediatric Emergency Medicine. 5th ed. Philadelphia, Pa.: Lippincott Williams & Wilkins; 2006. 295-306). Therefore, a topical ibuprofen formulation that can be accurately delivered through skin, particularly targeted for infants and toddlers, can have important health benefits. Besides ibuprofen (Fossel, U.S. Pat. No. 9,161,915), other nonsteroidal anti-inflammatory drug (NSAID) such as ketoprofen and naproxen or other drugs such as opioids (Chang, U.S. Pat. No. 4,956,171; El Khoury U.S. Pat. No. 5,866,143; Kanios et al. US 20060078604), estrogen (Carrara, U.S. Pat. No. 5,891,462), analgesics (El Khoury, U.S. Pat. No. 6,011,022), antidepressant, and antihypertensives (Urtti et al., U.S. Pat. No. 5,817,332), antitussive (Hoeck et al., U.S. Pat. No. 6,335,030) are also suitable for transdermal delivery.
Transdermal delivery of drugs with various topical compositions has been cited (Aungst et al., U.S. Pat. No. 4,626,539; Ebert et al., U.S. Pat. No. 5,152,997; El Khoury, U.S. Pat. No. 5,866,143; Carrara, U.S. Pat. No. 5,891,462; El Khoury, U.S. Pat. No. 6,011,022). Various transdermal drug delivery systems including transdermal patch have also been reported (Chang et al., U.S. Pat. No. 4,956,171; Fuisz U.S. Pat. No. 5,736,154; Urtti et al., U.S. Pat. No. 5,817,332; Chen et al., U.S. Pat. No. 5,902,603; Burton et al., U.S. Pat. No. 5,948,433; Hoeck et al., U.S. Pat. No. 6,335,030; Koch et al., U.S. Pat. No. 6,756,052; Ross, U.S. Pat. No. 8,696,637; Santini, Jr., et al., U.S. Pat. No. 7,537,590; Chen et al., U.S. Pat. No. 8,834,447; Fossel, U.S. Pat. No. 9,161,915; Kanios et al., US 20060078604). All of which are incorporated by reference herein.
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